Role of YKL-40 in the Microenvironment of Glioblastoma / 中国生物化学与分子生物学报

Glioblastoma (GBM) is the most common malignant tumor of the brain and central nervous system. The complex tumor microenvironment of glioblastoma is considered as the main challenge for clinical treatment of glioblastoma, also the main reason for the high recurrence rate and low survival rate of glioblastoma patients. YKL-40, a secreted protein, is associated with poor prognosis in many types of solid tumors. The expression of YKL-40 in serum and tumor tissues is significantly increased in high-grade gliomas, especially in glioblastoma patients. While this feature is not found in low-grade gliomas, indicating that the expression of YKL-40 is closely related to glioma grade and malignant development. Targeted therapy using YKL-40 antibody together with ionizing radiation has also been shown to synergistically inhibit tumor angiogenesis and malignant progression in glioblastoma patients. Based on the important role of YKL-40 in regulating the tumor microenvironment, this paper summarizes the research progress of YKL-40 in malignant tumors, and discusses the related role of YKL-40 in the occurrence and development of glioblastoma and its clinical application prospect.

Research progress of epithelial-to-mesenchymal(-like) transition in glioblastoma / 中国肿瘤临床

Epithelial-to-mesenchymal transition (EMT) is a normal process of cell physiological development in which the epithelial cells transform into mesenchymal cells through a specific program. EMT plays key roles in embryogenesis, tissue regeneration, and tu-mor progression. Recent research has shown the involvement of EMT-like in the tumorigenesis and progression (especially invasion and metastasis) of glioblastoma (GBM). This article reviews the molecular regulatory mechanisms of EMT (-like) including the main sig-naling pathways, EMT-factors, miRNA, cancer stem cells, hypoxia microenvironments, and therapy resistance in GBM.

Regulatory effect of hsa-miR-150-5p on malignant behaviors of glioblastoma U-251MG cells by targeting HIF1α / 中国肿瘤生物治疗杂志

@#Objective: To explore the effect and possible mechanisms of has-miR-150-5p targeting HIF1α to regulate malignant biological behaviors of glioblastoma (GBM) U-251MG cells. Methods: Real-time quantitative PCR (RT-PCR) was used to detect the expression of miR-150-5p and hypoxia inducible factor 1 (HIF1α) in U-251MG cells. Luciferase report assay was carried out to verify the biological relationship between miR-150-5p and HIF1α and their biological functions in U-251MG cells. The protein expressions of miR150-5pand HIF1α in U-251MG cells were detected by western blotting. The ability of cell migration was detected by wound healing test and cell invasion ability was detected by transwell test. Results: After miR-150-5p mimic transfection, the mRNA expression of HIF1α was significantly reduced in U-251MG cells (P<0.01). Bioinformatics prediction and luciferase reporter assay demonstrated that miR-150-5p down-regulated HIF1α through directly binding to HIF1α 3’-untranslated region (3’-UTR) (all P<0.05). In U-251MG cells, miR-150-5p over-expression significantly inhibited HIF1α expression, cell invasion and migration (all P<0.05). Conclusion: miR150-5p inhibits cell invasion and metastasis through negative regulation of HIF1α, indicating that miR-150-5p and HIF1α were both potential therapeutic targets for glioblastoma.

Differentiation between Glioblastoma and Primary Central Nervous System Lymphoma Using Dynamic Susceptibility Contrast-Enhanced Perfusion MR Imaging: Comparison Study of the Manual versus Semiautomatic Segmentation Method

BACKGROUND: Normalized cerebral blood volume (nCBV) can be measured using manual or semiautomatic segmentation method. However, the difference in diagnostic performance on brain tumor differentiation between differently measured nCBV has not been evaluated. PURPOSE: To compare the diagnostic performance of manually obtained nCBV to that of semiautomatically obtained nCBV on glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) differentiation. MATERIALS AND METHODS: Histopathologically confirmed forty GBM and eleven PCNSL patients underwent 3T MR imaging with dynamic susceptibility contrast-enhanced perfusion MR imaging before any treatment or biopsy. Based on the contrast-enhanced T1-weighted imaging, the mean nCBV (mCBV) was measured using the manual method (manual mCBV), random regions of interest (ROIs) placement by the observer, or the semiautomatic segmentation method (semiautomatic mCBV). The volume of enhancing portion of the tumor was also measured during semiautomatic segmentation process. T-test, ROC curve analysis, Fisher's exact test and multivariate regression analysis were performed to compare the value and evaluate the diagnostic performance of each parameter. RESULTS: GBM showed a higher enhancing volume (P = 0.0307), a higher manual mCBV (P = 0.018) and a higher semiautomatic mCBV (P = 0.0111) than that of the PCNSL. Semiautomatic mCBV had the highest value (0.815) for the area under the curve (AUC), however, the AUCs of the three parameters were not significantly different from each other. The semiautomatic mCBV was the best independent predictor for the GBM and PCNSL differential diagnosis according to the stepwise multiple regression analysis. CONCLUSION: We found that the semiautomatic mCBV could be a better predictor than the manual mCBV for the GBM and PCNSL differentiation. We believe that the semiautomatic segmentation method can contribute to the advancement of perfusion based brain tumor evaluation.